Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes in HIV-tuberculosis Co-infected Ugandan Adults
试验速览
- 阶段
- 4 期
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- clinical outcome
研究概览
简要总结
Tuberculosis (TB) is a leading cause of death in HIV-infected individuals. There are insufficient data correlating concentrations of anti-TB drugs with treatment response. We hypothesize that sub-therapeutic concentrations of anti-TB drugs are associated with inadequate TB treatment response to Mycobacterium tuberculosis.
详细描述
During the study periodic monitoring will be conducted to ensure that the protocol and Good Clinical Practices (GCPs) are being followed.The monitors may review source documents to confirm that the data recorded on CRFs is accurate. The study site may be subject to review by the Institutional Review Board (IRB) and/or appropriate regulatory authorities.
A CRF will be completed for each included subject and will be signed by the investigator or by an authorized staff member to attest that the data is true. Any corrections to entries made in the CRFs, source documents must be dated, initialed and explained (if necessary) and should not obscure the original entry. Qualit assurance will as also be performed regularly on the CRFs.
The primary end point will be analyzed using Time to event (cure, death, relapse etc)analysis and failure rates and hazard ratios will be calculated accordig to categorical drug concentrations with proposed cutt offs.
Secondary end points will be analysed using time to event for occurence of toxicities which will also be corelated to the drug concentrations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of a personally signed and dated informed consent
- •Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Age of ≥18 years
- •First episode of pulmonary TB i.e. proven or highly suspected TB considered for TB treatment qualifying for 6 months anti-Tb drugs regimen
- •Confirmed HIV-1 infection
排除标准
- •Unable to provide informed consent
- •Documented or highly suspected TB infection of any organs/systems other than the lung requiring TB treatment longer than 6 months
- •Previously treated for a mycobacterial infection (TB or atypical mycobacterial infection, active or latent)
- •Pregnancy or planned pregnancy within the next year
- •Unwillingness to perform pregnancy test
- •Decompensated liver disease and/or aminotransferases >5x ULN
- •GFR < 50 ml/min
- •Co-morbidities reducing life expectancy to <1 year (e.g. cancer)
- •Patient wishes to take part in another interventional study
研究组 & 干预措施
anti-tuberculosis drugs
Rifampicin, Isoniazid, Ethambutol, Pyrazinamide tablets 3 to 5 tablets once daily for 2 months followed by Rifampicin, Isoniazid 3 to 5 tablets once daily for 4 months
干预措施: Rifampicin, Isoniazid, Ethambutol, Pyrazinamide (Drug)
结局指标
主要结局
clinical outcome
时间窗: At the end of treatment (6 months after enrolmet)
To investigate the association between serum concentrations of antituberculosis drugs and tuberculosis treatment response in HIV-TB-co-infected individuals.
次要结局
- Cmax(At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation)
- Number of adverse events(2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation)
- ART trough levels(At 2 weeks, 8 weeks and 24 weeks after anti-tuberculosis drug initiation)
- Isoniazid Cmax(At 2 weeks, 8 weeks and 24 weeks)
研究者
Infectious Diseases Institute
Principal Investigator
Makerere University